Inpatient Insights
Study shows clinicians underutilize recently approved antibiotics
Despite FDA approval of seven next-generation antibiotics geared toward gram-negative infections between 2014 and 2019, clinicians still frequently treat resistant gram-negative infections with older, generic antibiotics that have suboptimal safety efficacy profiles. As part of the NIH Antimicrobial Resistance Outcome Research Initiative, researchers sought to determine use patterns of recently FDA-approved gram-negative antibiotics (ceftazidime–avibactam, ceftolozane–tazobactam, meropenem–vaborbactam, plazomicin, eravacycline, imipenem–relebactam–cilastatin, and cefiderocol) and identify factors associated with their preferential use in patients with gram-negative infections by pathogens displaying resistance to all first-line antibiotics, also known as difficult-to-treat (DTR) infections.
Results of the study, published online in Annals of Internal Medicine on April 19, 2024, showed that between January 2016 and March 2021, ceftolozane–tazobactam (approved in 2014) and ceftazidime–avibactam (approved in 2015) predominated new antibiotic usage, while subsequently approved gram-negative antibiotics saw relatively sluggish uptake.
Among adult patients with gram-negative infections in 619 U.S. hospitals, patients in 41.5% of studied DTR episodes were treated exclusively using traditional agents. “Reserve” antibiotics such as polymyxins, aminoglycosides, and tigecycline were used in 79.3% of episodes. Patients with bacteremia and chronic diseases were more likely to receive newer (vs. traditional) antibiotics for DTR infections, while those with do-not-resuscitate status, acute liver failure, and/or Acinetobacter baumannii complex or other nonpseudomonal nonfermenter pathogens were less likely to receive the newer antibiotics. Availability of susceptibility testing for new antibiotics increased probability of usage.
The authors note that future antibiotics with innovative mechanisms that target untapped pathogen niches, widely available susceptibility testing, and evidence demonstrating improved outcomes in resistant infections might enhance utilization. ■
Study shows higher risk of bleeding for patients with AFib using diltiazem
Diltiazem, a commonly prescribed ventricular rate–control medication for patients with AFib, is known to inhibit elimination of apixaban and rivaroxaban, possibly causing excess anticoagulation and increasing the risk for serious bleeding. A recent study published on April 15, 2024, in JAMA compared bleeding risk in patients with AFib using apixaban or rivaroxaban who subsequently began treatment with diltiazem with those who began treatment with metoprolol, an alternative rate-control medication not thought to inhibit direct oral anticoagulant elimination.
The retrospective cohort study involved over 200,000 Medicare beneficiaries aged 65 years or older with AFib who initiated apixaban or rivaroxaban use and who also began treatment with diltiazem or metoprolol between January 1, 2012, and November 29, 2020. The primary outcome was a composite of bleeding-related hospitalization and death with recent evidence of bleeding.
Results of the study showed that patients receiving diltiazem treatment had an increased risk for severe bleeding compared with patients receiving metoprolol, particularly for diltiazem doses exceeding 120 mg/day. ■
Updated SSC antibiotic timing recommendations appear effective
The Surviving Sepsis Campaign (SSC) released updated antibiotic timing recommendations in 2021 to provide guidance for clinicians caring for adult patients with sepsis or septic shock. The updated guidelines place an increased emphasis on improving the care of patients with sepsis after they are discharged from the intensive care unit and represent greater geographic and gender diversity than previous versions. Researchers from the University of Michigan, Wake Forest University, and Atrium Health conducted a retrospective cohort study at 12 hospitals in the southeastern United States to evaluate real-world implications of these updated SSC recommendations.
The study, published online in Critical Care Medicine on February 22, 2024, involved 166,559 adult patients treated in the emergency department for suspected serious infection between 2017 and 2021. The researchers determined the number and characteristics of patients affected by updated SSC recommendations for antibiotics initiation and found that 30% of the suspected infection cohort would be classified as “shock absent, possible infection” and thus eligible for the new 3-hour antibiotic recommendation; these patients had a conservative 5.5-hour time to antibiotics and low (2%) mortality. Patients categorized as “shock absent, probable infection” had a median time to antibiotics of 3.2 hours and mortality of 3%. Patients categorized as “shock present, probable infection” had a median time to antibiotics of 2.7 hours and mortality of 17%, and patients categorized as “shock present, possible infection” had a median time to antibiotics of 6.9 hours and mortality of 12%.
The researchers concluded that the data from their study support the updated SSC recommendations to align antibiotic timing targets with risk and probability stratifications and provide empirical support that clinicians and hospitals should not be held to 1-hour targets for patients without shock and with only possible sepsis. ■
Antifungal stewardship needed for patients with leukemia
Patients with leukemia are known to be at risk of invasive fungal infections, but the difficulty in diagnosing these infections can lead to overtreatment with antifungal agents. Researchers at University College London studied adults receiving treatment for acute myeloid leukemia between April 1, 2019, and October 14, 2022, to describe patterns and drivers of therapeutic antifungal prescribing in a large tertiary oncology center in the United Kingdom.
The study, published online on March 1, 2024, in Open Forum Infectious Diseases, showed that only 21.7% of patients receiving inpatient antifungal treatment had cases of proven/probable invasive fungal infections and that substantial antifungal use occurred in the absence of strong evidence of infection in patients receiving high-intensity first-line chemotherapy or approaching death. Indeterminate thoracic high-resolution CT reports of fungal infections were around eight times more likely to be followed by a new antifungal therapy episode than a negative report.
The authors note that antifungal stewardship remains challenging in the absence of reliable diagnostics, particularly in sicker patients, and they conclude that the proportion of antifungal therapy given for proven/probable infection is a new metric which will likely be useful to target antifungal stewardship programs. Reducing exposure to inappropriate antifungal prescribing is likely to improve patient safety. ■